Cholinergic Deafferentation of the Entorhinal Cortex in Rats Impairs Encoding of Novel But Not Familiar Stimuli in a Delayed Nonmatch-to-Sample Task

McGaughy, Jill; Koene, Randal A.; Eichenbaum, Howard; Hasselmo, Michael E.

doi:10.1523/jneurosci.2386-05.2005

Cited by 91 publications

(78 citation statements)

References 63 publications

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“…This finding is consistent with other findings and models suggesting a crucial role of cholinergic innervation of the EC in attentional processes in general, and in the acquisition/encoding of associations with novel stimuli in particular (Hasselmo, 2006;Hasselmo and McGaughy, 2004;Hasselmo and Stern, 2006;McGaughy et al, 2005;Ramirez et al, 2007). Notably, although cholinergic innervation of the EC has long been postulated to be involved in the attention to, and encoding of, novel stimuli, our results provide the first evidence that it also has a crucial role in the development of inattention to stimuli.…”

Section: Discussionsupporting

confidence: 92%

Differential Role of Muscarinic Transmission within the Entorhinal Cortex and Basolateral Amygdala in the Processing of Irrelevant Stimuli

Barak

Weiner

2010

Neuropsychopharmacol

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Cholinergic projections to the entorhinal cortex (EC) and basolateral amygdala (BLA) mediate distinct cognitive processes through muscarinic acetylcholine receptors (mAChRs). In this study, we sought to further differentiate the role of muscarinic transmission in these regions in cognition, using the latent inhibition (LI) phenomenon. LI is a cross-species phenomenon manifested as poorer conditioning to a stimulus experienced as irrelevant during an earlier stage of repeated non-reinforced pre-exposure to that stimulus, and is considered to index the ability to ignore, or to in-attend to, irrelevant stimuli. Given our recent findings that systemic administration of the mAChR antagonist scopolamine can produce two contrasting LI abnormalities in rats, ie, abolish LI under conditions yielding LI in non-treated controls, or produce abnormally persistent LI under conditions preventing its expression in non-treated controls, we tested whether mAChR blockade in the EC and BLA would induce LI abolition and persistence, respectively. We found that intra-EC scopolamine infusion (1, 10 mg per hemisphere) abolished LI when infused in pre-exposure or both pre-exposure and conditioning, but not in conditioning alone, whereas intra-BLA scopolamine infusion led to persistent LI when infused in conditioning or both stages, but not in pre-exposure alone. Although cholinergic innervation of the EC and BLA has long been implicated in attention to novel stimuli and in processing of motivationally significant stimuli, respectively, our results provide evidence that EC mAChRs also have a role in the development of inattention to stimuli, whereas BLA mAChRs have a role in re-attending to previously irrelevant stimuli that became motivationally relevant.

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Section: Discussionsupporting

confidence: 92%

Differential Role of Muscarinic Transmission within the Entorhinal Cortex and Basolateral Amygdala in the Processing of Irrelevant Stimuli

Barak

Weiner

2010

Neuropsychopharmacol

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“…Consistent with our study, McGaughy et al (2003) observed that cholinergic deafferentation of entorhinal cortex in rats caused deficits of performance in a delayed nonmatch-to-sample task with a 20 min delay when stimuli were novel but not when they were familiar. In the study presented here, we specifically focused on the effects of scopolamine on novel stimuli because previous neuroimaging studies demonstrated that activation of medial temporal cortices is strong for working memory with novel but not familiar stimuli (Ranganath and D'Esposito, 2001;Stern et al, 2001).…”

Section: Relationship To Behavioral Studiessupporting

confidence: 91%

“…These models suggested the hypothesis, confirmed here, that scopolamine should reduce delay activity related to encoding for subsequent memory. These models also suggested that loss of cholinergic modulation should impair memory for novel but not familiar stimuli, as demonstrated in another recent study (McGaughy et al, 2003).…”

Section: Relationship To Slice-recording Datamentioning

confidence: 52%

Scopolamine Reduces Persistent Activity Related to Long-Term Encoding in the Parahippocampal Gyrus during Delayed Matching in Humans

Schön

Atri²,

Hasselmo³

et al. 2005

J. Neurosci.

121

117

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Recent computational modeling and slice physiology studies have suggested that long-term encoding may depend on sustained spiking during brief memory delays in parahippocampal neurons, and that this persistent spiking activity is modulated by effects of acetylcholine at muscarinic receptors. Our recent functional magnetic resonance imaging (fMRI) study has shown that sustained parahippocampal delay period activity during delayed match-to-sample performance in healthy young individuals predicted subsequent memory of visual stimuli on a recognition memory assessment 20 min later (Schon et al., 2004). The current study combined this fMRI paradigm with a pharmacological manipulation to test whether this long-term encoding-related delay activity is reduced in subjects who receive the muscarinic cholinergic antagonist scopolamine before fMRI scanning. Subsequent memory was predicted by sustained activity during brief memory delays bilaterally in the perirhinal/entorhinal cortex, in the right posterior parahippocampal and mid-fusiform gyri, and in the hippocampal body in healthy young individuals without a scopolamine challenge. This activity was reduced in subjects receiving scopolamine. The results are consistent with computational modeling data and behavioral pharmacological studies, suggesting that long-term encoding-related activity may be reduced if cholinergic receptors are blocked by scopolamine.

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“…This is in keeping with the results of a large number of studies that characterized the morphological and behavioral effects of the 192 IgG-saporin injections. Reduction of the cortical thickness and cholinergic innervation (Robertson et al, 1998;Koh et al, 2005) associated with more or less pronounced impairment of visual attention and working memory (Leanza et al, 1996;Pappas et al, 2005;McGaughy et al, 2005) have been described. Yet, in contrast to robust modification of activity in neonates, the adult cortical activity is less impaired by 192 IgG-saporin (Wenk et al, 1994;Holschneider et al, 1999).…”

Section: Cholinergic Control Of V1 Spindle Burstsmentioning

confidence: 99%

Cholinergic Modulation of Spindle Bursts in the Neonatal Rat Visual CortexIn Vivo

Hanganu¹,

Staiger²,

Ben-Ari³

et al. 2007

J. Neurosci.

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Acetylcholine (ACh) is known to shape the adult neocortical activity related to behavioral states and processing of sensory information. However, the impact of cholinergic input on the neonatal neuronal activity remains widely unknown. Early during development, the principal activity pattern in the primary visual (V1) cortex is the intermittent self-organized spindle burst oscillation that can be driven by the retinal waves. Here, we assessed the relationship between this early activity pattern and the cholinergic drive by either blocking or augmenting the cholinergic input and investigating the resultant effects on the activity of the rat visual cortex during the first postnatal week in vivo. Blockade of the muscarinic receptors by intracerebroventricular, intracortical, or supracortical atropine application decreased the occurrence of V1 spindle bursts by 50%, both the retina-independent and the optic nerve-mediated spindle bursts being affected. In contrast, blockade of acetylcholine esterase with physostigmine augmented the occurrence, amplitude, and duration of V1 spindle bursts. Whereas direct stimulation of the cholinergic basal forebrain nuclei increased the occurrence probability of V1 spindle bursts, their chronic immunotoxic lesion using 192 IgG-saporin decreased the occurrence of neonatal V1 oscillatory activity by 87%. Thus, the cholinergic input facilitates the neonatal V1 spindle bursts and may prime the developing cortex to operate specifically on relevant early (retinal waves) and later (visual input) stimuli.

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Cholinergic Deafferentation of the Entorhinal Cortex in Rats Impairs Encoding of Novel But Not Familiar Stimuli in a Delayed Nonmatch-to-Sample Task

Cited by 91 publications

References 63 publications

Differential Role of Muscarinic Transmission within the Entorhinal Cortex and Basolateral Amygdala in the Processing of Irrelevant Stimuli

Differential Role of Muscarinic Transmission within the Entorhinal Cortex and Basolateral Amygdala in the Processing of Irrelevant Stimuli

Scopolamine Reduces Persistent Activity Related to Long-Term Encoding in the Parahippocampal Gyrus during Delayed Matching in Humans

Cholinergic Modulation of Spindle Bursts in the Neonatal Rat Visual CortexIn Vivo

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